HIV-1/AIDS continues to be a global problem as no cure exists. While highly active anti-retroviral therapy is available to reduce viral loads in patients and delay the onset of disease, these treatments are costly, have numerous side effects and face a constantly mutating virus. Recently, some researchers have focused on the role cellular factors play on specific steps of HIV-1 replication in order to develop new targets for anti- retroviral therapy. One such new area of study focuses on the misunderstood process of HIV-1 core uncoating. Uncoating is defined specifically as the disassembly of the viral conical core and subsequent release of the viral genome. The Aiken laboratory has established that HIV-1 core disassembly is a highly sensitive process susceptible to small alterations in capsid stability. These alterations in core stability did not disrupt the conical structure but impaired reverse transcriptase activity and attenuated HIV-1 replication. The objective of this research is to identify the viral and cellular factors that play a role in core disassembly in order to achieve a better understanding of HIV-1 biology. This objective will be achieved by addressing three specific aims: 1. To identify a cellular factor that plays a role in HIV-1 core disassembly. 2. To determine the biological significance of this factor on HIV-1 infection. 3. To determine the role of core associated viral MA in HIV-1 uncoating and identify specific residues in MA responsible for uncoating. Completion of these three specific aims should open up a new area of research into the early post entry steps of HIV-1 replication with the possibility for identifying novel targets of anti-retroviral therapy. [unreadable] [unreadable] [unreadable]